"The U.S. Food and Drug Administration today approved Breo Ellipta (fluticasone furoate and vilanterol inhalation powder) for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary di"...
- Patient Information:
Details with Side Effects
Long-acting beta2-adrenergic agonists, such as ARCAPTA NEOHALER, increase the risk of asthma-related death. ARCAPTA NEOHALER is not indicated for the treatment of asthma [See BOXED WARNING and WARNING AND PRECAUTIONS].
Clinical Trials Experience in Chronic Obstructive Pulmonary Disease
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The ARCAPTA NEOHALER safety database reflects exposure of 2516 patients to ARCAPTA NEOHALER at doses of 75 mcg or greater for at least 12 weeks in six confirmatory randomized, double-blind, placebo and active-controlled clinical trials. In these trials, 449 patients were exposed to the recommended dose of 75 mcg for up to 3 months, and 144, 583 and 425 COPD patients were exposed to a dose of 150, 300 or 600 mcg for one year, respectively. Overall, patients had a mean pre-bronchodilator forced expiratory volume in one second (FEV1) percent predicted of 54%. The mean age of patients was 64 years, with 47% of patients aged 65 years or older, and the majority (88%) was Caucasian.
In these six clinical trials, 48% of patients treated with any dose of ARCAPTA NEOHALER reported an adverse reaction compared with 43% of patients treated with placebo. The proportion of patients who discontinued treatment due to adverse reaction was 5% for ARCAPTA NEOHALER-treated patients and 5% for placebo-treated patients. The most common adverse reactions that lead to discontinuation of ARCAPTA NEOHALER were COPD and dyspnea.
Table 1 displays adverse drug reactions reported by at least 2% of patients (and higher than placebo) during a 3 month exposure at the recommended 75 mcg once daily dose. Adverse drug reactions are listed according to MedDRA (version 13.0) system organ class and sorted in descending order of frequency.
Table 1: Number and frequency of adverse drug reactions greater
than 2% (and higher than placebo) in COPD patients exposed to ARCAPTA NEOHALER
75 mcg for up to 3 months in multiple dose, controlled trials
|Indacaterol 75 mcg once daily
n=449 n (%)
n=445 n (%)
|Respiratory, thoracic and mediastinal disorders|
|Cough||29 (6.5)||20 (4.5)|
|Oropharyngeal pain||10 (2.2)||3 (0.7)|
|Infections and infestations|
|Nasopharyngitis||24 (5.3)||12 (2.7)|
|Nervous system disorders|
|Headache||23 (5.1)||11 (2.5)|
|- Nausea||11 (2.4)||4 (0.9)|
In these trials the overall frequency of all cardiovascular adverse reactions was 2.5% for ARCAPTA NEOHALER 75 mcg and 1.6% for placebo during a 3 month exposure. There were no frequently occurring specific cardiovascular adverse reactions for ARCAPTA NEOHALER 75 mcg (frequency at least 1% and greater than placebo).
Additional adverse drug reactions reported in greater than 2% (and higher than on placebo) in patients dosed with 150, 300 or 600 mcg for up to 12 months were as follows:
- Musculoskeletal and connective tissue disorders: muscle spasm, musculoskeletal pain
- General disorders and administration site conditions: edema peripheral
- Metabolism and nutrition disorder: diabetes mellitus, hyperglycemia
- Infections and infestations: sinusitis, upper respiratory tract infection
Cough experienced post-inhalation
In the clinical trials, health care providers observed during clinic visits that an average of 24% of patients experienced a cough on at least 20% of visits following inhalation of the recommended 75 mcg dose of ARCAPTA NEOHALER compared to 7% of patients receiving placebo. The cough usually occurred within 15 seconds following inhalation and lasted for no more than 15 seconds. Cough following inhalation in clinical trials was not associated with bronchospasm, exacerbations, deteriorations of disease or loss of efficacy.
Clinical Trials Experience in Asthma
In a 6-month randomized, active controlled asthma safety trial, 805 adult patients with moderate to severe persistent asthma were treated with ARCAPTA NEOHALER 300 mcg (n=268), ARCAPTA NEOHALER 600 mcg (n=268), and salmeterol (n=269), all concomitant with inhaled corticosteroids, which were not co-randomized. Of these patients, there were 2 respiratory-related deaths in the ARCAPTA NEOHALER 300 mcg dose group. There were no deaths in the ARCAPTA NEOHALER 600 mcg dose group or in the salmeterol active control group. Serious adverse reactions related to asthma exacerbation were reported for 2 patients in the indacaterol 300 mcg group, 3 patients in the indacaterol 600 mcg group, and no patients in the salmeterol active control group.
In addition, a two-week dose-ranging trial was conducted in 511 adult patients with mild persistent asthma taking inhaled corticosteroids. No deaths, intubations, or serious adverse reactions related to asthma exacerbation were reported in this trial.
The following adverse reactions have been identified during worldwide post-approval use of indacaterol, the active ingredient in ARCAPTA NEOHALER. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are: tachycardia/heart rate increase/palpitations, pruritus/rash and dizziness.
Read the Arcapta Neohaler (indacaterol inhalation powder) Side Effects Center for a complete guide to possible side effects
If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of ARCAPTA NEOHALER may be potentiated [see WARNINGS AND PRECAUTIONS].
Xanthine Derivatives, Steroids, or Diuretics
Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of ARCAPTA NEOHALER [see WARNINGS AND PRECAUTIONS].
Non-Potassium Sparing Diuretics
The ECG changes or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the betaagonist is exceeded. Although the clinical relevance of these effects is not known, caution is advised in the coadministration of ARCAPTA NEOHALER with non-potassium-sparing diuretics.
Monoamine Oxidase Inhibitors, Tricyclic Antidepressants, QTc Prolonging Drugs
Indacaterol, as with other beta2-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs known to prolong the QTc interval because the action of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval may have an increased risk of ventricular arrhythmias.
Beta-adrenergic receptor antagonists (beta-blockers) and ARCAPTA NEOHALER may interfere with the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, e.g. as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
Inhibitors of Cytochrome P450 3A4 and P-gp Efflux Transporter
Drug interaction studies were carried out using potent and specific inhibitors of CYP3A4 and P-gp (i.e., ketoconazole, erythromycin, verapamil and ritonavir). The data suggest that systemic clearance is influenced by modulation of both P-gp and CYP3A4 activities and that the 1.9-fold AUC0-24 increase caused by the strong dual inhibitor ketoconazole reflects the impact of maximal combined inhibition. ARCAPTA NEOHALER was evaluated in clinical trials for up to one year at doses up to 600 mcg. No dose adjustment is warranted at the 75 mcg dose.
Read the Arcapta Neohaler Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 10/15/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Arcapta Neohaler Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.